Asymmetric hydrogenation of alkenes using chiral iridium complexes

Abstract

The invention relates to the (stereoselective) hydrogenation of carbon-carbon double bonds in compounds having at least one such bond, e.g., isoprenoids, non-cyclic sesquiterpenes, tocomonoenols, tocodienols, tocotrienols or derivatives thereof, as well as to the (stereoselective) hydrogenation of parts/extracts of plant oils containing such tocotrienols or derivatives thereof, in the presence of a chiral Ir complex as the catalyst, whereby preferably one stereoisomer is manufactured in an excess.

The invention claimed is: 
     
       1. Process for the manufacture of a compound of the formula I 
       
         
           
           
               
               
           
         
         wherein the position labelled with the asterisk is an asymmetry center and  R 1  is a group of the formula 
       
       
         
           
           
               
               
           
         
         with R 2  being a hydroxyl group or a protected hydroxyl group, and R 3  and R 4  being independently from each other hydrogen or methyl, and n being an integer from 1 to 10, 
         comprising the step of hydrogenating a compound of the formula II 
       
       
         
           
           
               
               
           
         
         wherein at least one carbon-carbon double bond is present, and wherein the dotted lines represent the possible positions of such (facultative) carbon-carbon double bonds; and R 1  and n are as above, 
         in the presence of a chiral iridium (Ir) complex as the catalyst selected from the group consisting of Ir complexes of the formula III, IV, V, VI, VII, VIII, IX, X, XI or XV, and their enantioners of formula: 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein R, X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , X 15 , X 16 , X 17 , X 18 , X 19 , X 20 , X 21  and X 22  are independently from each other hydrogen, C 1-4 -alkyl, C 5-7 -cycloalkyl, phenyl, phenyl substituted with one to three C 1-4 -alkyl, C 1-4 -alkoxy and/or C 1-4 -perfluoroalkyl groups, benzyl, 1-naphthyl, or ferrocenyl, 
         the anion Y is a weakly coordinating anion, n is 1 to 2, and 
         “o-Tol” means ortho-tolyl, “Ph” means phenyl, “TBDMS” means tert-butyl-dimethylsilyl, “p-Tol” means para-tolyl, “BAr F ” means tetra(3,5-bis(trifluoromethyl)phenyl)borate, 
         and the Ir complexes of the formula III to XI and XV, and the corresponding enantiomeric formula whereby the cyclooctadiene ligand is replaced by ethene or norbornadiene. 
       
     
     
       2. The process according to  claim 1 , wherein the compound of the formula II is a tocomonoenol, a tocodienol, or a tocotrienol which is hydrogenated to the corresponding compound of the formula I, wherein the tocomonoenol, the tocodienol, and the tocotrienol are of the formula XIII, 
       
         
           
           
               
               
           
         
         wherein the dotted bonds are optional and at least one of the dotted bonds is present, and wherein R 2  is a hydroxyl group or a protected hydroxyl group and R 3  and R 4  are independently from each other hydrogen or methyl. 
       
     
     
       3. The process according to  claim 1 , wherein the amount of the catalyst is from about 0.05 to about 5 mol %, based on the amount of the compound of the formula II. 
     
     
       4. The process according to  claim 1 , wherein the compound of the formula II is selected from the group consisting of (2R,3′E,7′E)-α-tocotrienol, (2R,3′E,7′E)-β-tocotrienol, (2R,3′E,7′E)-γ-tocotrienol, (2R,3′E,7′E)-δ-tocotrienol, (2R,3′E,7′E)-α-tocotrienol methyl ether, (2R,3′E,7′E)-α-tocotrienol methoxymethylether, (2R,3′E,7′E)-α-tocotrienol methoxyethylether, (2R,3′E,7′E)-α-tocotrienol tetrahydropyranyl ether, (2R,3′E,7′E)-α-tocotrienol ethoxyethyl ether, (2R,3′E,7′E)-α-tocotrienol methoxyethoxyethyl ether, (2R,3′E,7′E)-α-tocotrienol acetic acid ester, (2R,3′E,7′E)-α-tocotrienol formic acid ester, (2R,3′E,7′E)-α-tocotrienol succinic acid monoester, (2R,3′E,7′E)-α-tocotrienol propionic acid ester, (2R,3′E,7′E)-α-tocotrienol benzoic acid ester, (2R,3′E,7′E)-α-tocotrienol palmitic acid ester, (2R,3′E,7′E)-β-tocotrienol methyl ether, (2R,3′E,7′E)-β-tocotrienol methoxymethylether, (2R,3′E,7′E)-β-tocotrienol methoxyethylether, (2R,3′E,7′E)-β-tocotrienol tetrahydropyranyl ether, (2R,3′E,7′E)-β-tocotrienol ethoxyethyl ether, (2R,3′E,7′E)-β-tocotrienol methoxyethoxyethyl ether, (2R,3′E,7′E)-β-tocotrienol acetic acid ester, (2R,3′E,7′E)-β-tocotrienol formic acid ester, (2R,3′E,7′E)-β-tocotrienol succinic acid monoester, (2R,3′E,7′E)-β-tocotrienol propionic acid ester, (2R,3′E,7′E)-β-tocotrienol benzoic acid ester, (2R,3′E,7′E)-β-tocotrienol palmitic acid ester, (2R,3′E,7′E)-γ-tocotrienol methyl ether, (2R,3′E,7′E)-γ-tocotrienol methoxymethylether, (2R,3′E,7′E)-γ-tocotrienol methoxyethylether, (2R,3′E,7′E)-γ-tocotrienol tetrahydropyranyl ether, (2R,3′E,7′E)-γ-tocotrienol ethoxyethyl ether, (2R,3′E,7′E)-γ-tocotrienol methoxyethoxyethyl ether, (2R,3′E,7′E)-γ-tocotrienol acetic acid ester, (2R,3′E,7′E)-γ-tocotrienol formic acid ester, (2R,3′E,7′E)-γ-tocotrienol succinic acid monoester, (2R,3′E,7′E)-γ-tocotrienol propionic acid ester, (2R,3′E,7′E)-γ-tocotrienol benzoic acid ester, (2R,3′E,7′E)-γ-tocotrienol palmitic acid ester, (2R,3′E,7′E)-δ-tocotrienol methyl ether, (2R,3′E,7′E)-δ-tocotrienol methoxymethylether, (2R,3′E,7′E)-δ-tocotrienol methoxyethylether, (2R,3′E,7′E)-δ-tocotrienol tetrahydropyranyl ether, (2R,3′E,7′E)-δ-tocotrienol ethoxyethyl ether, (2R,3′E,7′E)-δ-tocotrienol methoxyethoxyethyl ether, (2R,3′E,7′E)-δ-tocotrienol acetic acid ester, (2R,3′E,7′E)-δ-tocotrienol formic acid ester, (2R,3′E,7′E)-δ-tocotrienol succinic acid monoester, (2R,3′E,7′E)-δ-tocotrienol propionic acid ester, (2R,3′E,7′E)-δ-tocotrienol benzoic acid ester, (2R,3′E,7′E)-δ-tocotrienol palmitic acid ester, and mixtures thereof, as well as any part or extract of a plant oil containing at least a compound of said group. 
     
     
       5. Process according to  claim 1 , wherein the compound of the formula II is (2R,3′E,7′E)-α-tocotrienyl acetate, which is hydrogenated to a mixture of the four diastereoisomers (2R,4′S,8′R)-α-tocopheryl acetate, (2R,4′R,8′S)-α- tocopheryl acetate, (2R,4′R,8′R)-α-tocopheryl acetate and (2R,4′S,8′S)-α-tocopheryl acetate in the presence of the chiral Ir complex selected from the group consisting of Ir complexes of the formula E1, E2, E7, E15 and H1 and the enantioners thereof, wherein one diastereoisomer is manufactured in excess, 
       
         
           
           
               
               
           
         
         and “o-Tol” means o-tolyl, “Ph” means phenyl, “BAr F ” is tetra(3,5-bis(trifluoromethyl)phenyl)borate, “n-Bu” means=n-butyl, and “Me” means methyl. 
       
     
     
       6. Process according to  claim 1 , wherein the compound of the formula II is (2R,3′E,7′E)-γ-tocotrienyl acetate which is hydrogenated to a mixture of the four diastereoisomers (2R,4′S,8′R)-γ-tocopheryl acetate, (2R,4′R,8′S)-γ-tocopheryl acetate, (2R,4′R,8′R)-γ-tocopheryl acetate and (2R,4′S,8′S)-γ-tocopheryl acetate in the presence of the chiral Ir complex C1, D1, E1, F1 or H1 
       
         
           
           
               
               
           
         
         whereby “Ph” means phenyl, “Bn” means benzyl, “BAr F ” is tetra(3,5-bis(trifluoromethyl)phenyl)borate[B(3,5-C 6 H 3 (CF 3 ) 2 ) 4 ] − , “o-Tol” means o-tolyl, and “TBDMS” means tert-butyl-dimethyl silyl, 
         as the catalyst, whereby one diastereoisomer is manufactured in excess. 
       
     
     
       7. A process for the manufacture of a hydrogenated part or extract of a plant oil, comprising the step of hydrogenating the part or extract of the plant oil comprising at least a tocotrienol of formula A 
       
         
           
           
               
               
           
         
         in the presence of a chiral Ir complex as the catalyst with R 2  being a hydroxyl group or a protected hydroxyl group, and R 3  and R 4  being independently from each other hydrogen or methyl. 
       
     
     
       8. The process according to  claim 7 , wherein the tocotrienol of formula A is hydrogenated to a tocopherol of formula B 
       
         
           
           
               
               
           
         
         with R 2  being a hydroxyl group or a protected hydroxyl group, and R 3  and R 4  being independently from each other hydrogen or methyl. 
       
     
     
       9. The process according to  claim 7 , wherein the chiral Ir complex is selected of the group consisting of Ir complexes of one of the formulae III to XI and XV and their corresponding enantiomers of formula: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein R, X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , X 15 , X 16 , X 17 , X 18 , X 19 , X 20  X 21  and X 22  are independently from each other hydrogen, C 1-4 -alkyl, C 5-7 -cycloalkyl, phenyl, phenyl substituted with one to three C 1-4 -alkyl, C 1-4 -alkoxy and/or C 1-4 -perfluoroalkyl groups, benzyl, 1-naphthyl, or ferrocenyl, 
         the anion Y is a weakly coordinating anion, n is 1 or 2, and 
         “o-Tol” means ortho-tolyl, “Ph” means phenyl, “TBDMS” means tert-butyl-dimethylsilyl, “p-Tol” means para-tolyl, “BAr F ” means tetra(3,5-bis(trifluoromethyl)phenyl)borate 
         or the Ir complex is of the formula III to XI or XV, or the corresponding enantiomeric formula whereby the cyclooctadiene ligand is replaced by ethene or norbornadiene. 
       
     
     
       10. The process according to  claim 1 , wherein n is 1-3. 
     
     
       11. The process according to  claim 3 , wherein the amount of catalyst is from about 0.09 to about 2.5 mol %. 
     
     
       12. The process according to  claim 3 , wherein the amount of catalyst is from about 0.1 to about 2.0 mol %. 
     
     
       13. The process according to  claim 5 , wherein the stereoisomer (2R,4′R,8′R)-α-tocopheryl acetate is at least 55%. 
     
     
       14. The process according to  claim 5 , wherein the stereoisomer (2R,4′R,8′R)-α-tocopheryl acetate is at least 90%. 
     
     
       15. The process according to  claim 6 , wherein the diastereoisomer is present in an amount of at least 45%. 
     
     
       16. The process according to  claim 7 , wherein the plant oil is palm oil.